Chandra Dass

Genome-wide association study of smoking behaviours in patients with COPD

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10−5 for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions

The real‐world tolerability of pirfenidone and nintedanib in non‐clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co‐morbidities or baseline characteristics that exclude them from clinical trial participation.

Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition.

Bronchiectasis manifests as recurrent respiratory infections and reduced lung function. Airway dilation, which is measured as the ratio of the diameters of the bronchial lumen (B) and adjacent pulmonary artery (A), is a defining radiological feature of bronchiectasis. A challenge to equating the bronchoarterial (BA) ratio to disease severity is that the diameters of airway and vessel in health are not established. We sought to explore the variability of BA ratio in never‐smokers without pulmonary disease and its associations with lung function.

Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome

Background Acute exacerbation of idiopathic pulmonary fibrosis (AE‐IPF) has an expected median survival of 3 months. Lung transplantation is a potentially lifesaving therapy for AE‐IPF. However, the current knowledge of transplantation outcomes during AE‐IPF is limited to a few small retrospective studies, reporting only 1‐year post‐transplantation survival. Methods Study population included patients with IPF consecutively listed for lung transplantation at a single institution between the years 2012 and 2016. We collected lung allocation score (LAS), hospitalization, and survival data. The primary outcome was survival among patients transplanted during stable IPF vs during AE‐IPF. Results Of 89 patients with IPF listed for lung transplantation, 52 were transplanted during stable IPF and 37 were hospitalized due to AE‐IPF. Of these 37 patients, nine died before transplantation, and 28 were transplanted during AE‐IPF. Fifty percent of patients transplanted during AE‐IPF died in a mean follow‐up of 1.6 ± 1.2 years compared with 12% of patients transplanted during stable IPF who died in a mean follow‐up of 2.6 ± 1.2 years. The Kaplan‐Meier survival curves post‐transplantation after 1 and 3 years for patients who were transplanted during stable IPF were 94% and 90% vs 71% and 60% in patients who were transplanted during AE‐IPF (P = .0001). LAS above 80 conferred a 3‐year hazard ratio for mortality of 5.7 vs LAS lower than 80 (95% CI, 2.33‐14.0; P < .0005). Conclusions Patients with IPF transplanted during AE‐IPF had significantly worse short‐term and long‐term survival compared with patients transplanted during stable IPF. Patients with AE‐IPF and very high LAS may not experience the survival advantage expected from lung transplantation.

Radiologic Imaging in the Critically Ill Patient

After studying this chapter, you should be able to do the following: Develop a systematic approach for the interpretation of ICU chest radiographs. Be aware of the most common causes of abnormal pulmonary opacities and air collections on ICU chest radiographs. Know when to obtain a portable chest radiograph (PCR), thoracic computed tomography (CT), sonography, and ventilation.perfusion (VP) scans in ICU patients. Be familiar with the roles of abdominal and pelvic imaging procedures, including plain film examinations, barium contrast studies, US, MRI, and CT in the assessment of the ICU patient with acute abdominal and pelvic disease. Be aware of the relative merits of CT and MR imaging in the evaluation of the ICU patient with suspected acute neurologic abnormalities.

Rapidly progressing lepidic pulmonary metastases from a treated poorly differentiated hepatocellular carcinoma demonstrating new pathologic features of cholangiocarcinoma: A potential diagnostic pitfall that may mimic pneumonia

Although the lung is a common site for metastatic disease from extrathoracic malignancies, a pattern of lepidic growth of these metastases is considered rare. A 67-year-old man with a history of partial hepatectomy for hepatocellular carcinoma (HCC) presented to our hospital with dyspnea and a nonproductive cough. Chest radiographs and computed tomography imaging demonstrated consolidation in the right upper lobe and an ipsilateral pleural effusion. Findings were initially suspected to be secondary to infection, given the radiographic appearance and the rapid development from a normal computed tomography 3 months previously. However, the patient did not have convincing clinical evidence of pneumonia, and after little change after antibiotic therapy, a thoracentesis and pleural biopsy were performed that were positive for malignancy. Although immunostaining and morphology closely resembled the patients primary HCC, new pathologic features of cholangiocarcinoma were found. We herein report the first case of rapidly progressing lepidic pulmonary metastases from an HCC that dedifferentiated into a hepatocholangiocarcinoma.

EXPRESS: Case series of seven women with uterine fibroids associated with venous thromboembolism and chronic thromboembolic disease

Uterine fibroids have been described as an associate to acute venous thromboembolism (VTE), with case reports showing an association between large uterine fibroids, acute deep venous thrombosis (DVT), and acute pulmonary embolism (PE). However, there is little known about the association or causation between uterine fibroids, chronic thromboembolic disease (CTED), and chronic thromboembolic pulmonary hypertension (CTEPH). We report on six women with uterine fibroids and CTEPH, as well as one woman with CTED, all of whom presented with exertional dyspnea, lower extremity swelling, and in the cases of CTEPH, clinical, echocardiographic, and hemodynamic evidence of pulmonary hypertension and right heart failure. Compression of the pelvic veins by fibroids was directly observed with invasive venography or contrast-enhanced computed tomography in five cases. All seven women underwent pulmonary thromboendarterectomy (PTE) followed by marked improvement in functional, clinical, and hemodynamic status.

Endobronchial Coils Versus Lung Volume Reduction Surgery or Medical Therapy for Treatment of Advanced Homogenous Emphysema

Rationale: Bronchoscopic lung volume reduction utilizing shape-memory nitinol endobronchial coils (EBC) may be safer and more effective in severely hyperinflated homogeneous emphysema compared to medical therapy or lung volume reduction surgery (LVRS). Methods: The effect of bilateral EBC in patients with homogeneous emphysema on spirometry, lung volumes and survival was compared to patients with homogeneous emphysema randomized in the National Emphysema Treatment Trial (NETT) to LVRS or medical therapy. NETT participants were selected to match EBC participants in age, baseline spirometry, and gender. Outcomes were compared from baseline, at 6 and 12 months. Results: There were no significant baseline differences in gender in the EBC, NETT-LVRS or medical treatment patients. At baseline no differences existed between EBC and NETT-LVRS patients in forced expiratory volume in 1 second ( FEV1) or total lung capacity (TLC) %-predicted; residual volume (RV) and diffusing capacity of the lung for carbon monoxide (DLco) %-predicted were higher in the EBC group compared to NETT-LVRS (p < 0.001). Compared to the medical treatment group, EBC produced greater improvements in FEV1 and RV but not TLC at 6 months. FEV1 and RV in the EBC group remained significantly improved at 12-months compared to the medical treatment group. While all 3 therapies improved quality of life, survival at 12 months with EBC or medical therapy was greater than NETT-LVRS. Conclusion: EBC may be a potential therapeutic option in patients with severe homogeneous emphysema and hyperinflation who are already receiving optimal medical treatment.

Visual Estimate of Coronary Artery Calcium Predicts Cardiovascular Disease in COPD

BACKGROUND: COPD is associated with cardiovascular disease (CVD), and coronary artery calcification (CAC) provides additional prognostic information. With increasing use of nongated CT scans in clinical practice, this study hypothesized that the visual Weston CAC score would perform as well as the Agatston score in predicting prevalent and incident coronary artery disease (CAD) and CVD in COPD. METHODS: CAC was measured by using Agatston and Weston scores on baseline CT scans in 1,875 current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study. Baseline cardiovascular disease and incident cardiac events on longitudinal follow‐up were recorded. Accuracy of the CAC scores was measured by using receiver‐operating characteristic analysis, and Cox proportional hazards analyses were used to estimate the risk of incident cardiac events. RESULTS: CAD was reported by 133 (7.1%) subjects at baseline. A total of 413 (22.0%) and 241 (12.9%) patients had significant CAC according to the Weston (≥ 7) and Agatston (≥ 400) scores, respectively; the two methods were significantly correlated (r = 0.84; P < .001). Over 5 years of follow‐up, 127 patients (6.8%) developed incident CVD. For predicting prevalent CAD, c‐indices for the Weston and Agatston scores were 0.78 and 0.74 and for predicting incident CVD, they were 0.62 and 0.61. After adjustment for age, race, sex, smoking pack‐years, FEV1, percent emphysema, and CT scanner type, a Weston score ≥ 7 was associated with time to first acute coronary event (hazard ratio, 2.16 [95% CI, 1.32 to 3.53]; P = .002), but a Agatston score ≥ 400 was not (hazard ratio, 1.75 [95% CI, 0.99‐3.09]; P = .053). CONCLUSIONS: A simple visual score for CAC performed well in predicting incident CAD in smokers with and without COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

High-Resolution CT Findings of Obstructive and Restrictive Phenotypes of Chronic Lung Allograft Dysfunction: More Than Just Bronchiolitis Obliterans Syndrome

OBJECTIVE The purpose of this article is to review the high-resolution CT characteristics of individual obstructive and restrictive chronic lung allograft dysfunction (CLAD) phenotypes to aid in making accurate diagnoses and guiding treatment. CONCLUSION Long-term survival and function after lung transplant are considerably worse compared with after other organ transplants. CLAD is implicated as a major limiting factor for long-term graft viability. Historically thought to be a single entity, bronchiolitis obliterans syndrome, CLAD is actually a heterogeneous group of disorders with distinct subtypes.